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Arl4A interacts with Robo1 to promote cell migration via up‐regulating Cdc42 activation
Author(s) -
Lee FangJen Scott,
Chiang TsaiShin,
Chen ChiehHsin,
Tsai MengChen,
Jang LiTing
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb145
Subject(s) - cdc42 , cell migration , microbiology and biotechnology , rac1 , actin cytoskeleton , small gtpase , chemistry , cell , motility , gtpase , biology , cytoskeleton , signal transduction , biochemistry
Cell migration is a highly regulated event that is initiated by protrusion of the cell membrane and actin reorganization. Robo1, a single‐pass transmembrane receptor, is crucial for neuronal guidance and cell migration via activating Cdc42 GTPase. ADP‐ribosylation factor (Arf)‐like 4A (Arl4A), one of Arf small GTPases, functions in cell morphology, cell migration, and actin cytoskeleton remodelling; however, the molecular mechanisms for Arl4A in cell migration is not clear. Here, we report that Arl4A binding to Robo1 modulates cell migration via promoting Cdc42 activation. We found that Arl4A interacts with Robo1 in a GTP‐dependent manner and residual 1394‐1399 of Robo1 is both required and sufficient for this interaction. Arl4A‐Robo1 interaction is essential for Arl4A‐induced cell migration and Cdc42 activation. We also showed that Arl4A binding to Robo1 decreases the association of a Cdc42‐GAP srGAP1 to Robo1. Furthermore, Slit2/Robo1 binding decreases Arl4A‐Robo1 interaction in vivo. Thus, our study reveals a novel mechanism that Arl4A participates in Slit2/Robo1 signaling on modulating cell motility via up‐regulating Cdc42 activation. Support or Funding Information NHRI‐EX106‐10601B1